Transamidation and amide metathesis represent novel means of producing polyamides and small carboxamide-containing molecules. These reactions are attractive from the design perspective because their starting materials, amides and amines, can be easily obtained with highly diverse functionalities. An important aspect of using transamidation or amide metathesis to synthesize polyamides and small molecules is the production of new, highly-stable molecules with useful properties. Further, the most stable component of a random mixture of molecules can be selected and amplified using the principles of dynamic covalent chemistry (DCC). (For reviews, see Sanders et al. (2002) “Dynamic Covalent Chemistry,” Angew. Chemie Intl. Edn., 41:898.) In amide-based DCC, alternative amide linkages equilibrate with one another, thereby giving rise to novel products. In short, in a dynamic combinatorial library of amides or amines, all compounds are in thermodynamic equilibrium, allowing the library composition to adapt to external influences. Thus, for example, binding forces between a ligand and its receptor can be used to select, stabilize and, thereby amplify the best amide-containing or amine-containing inhibitor in the library. In this scenario, ligand-induced amplification can be used to identify amide- or amine-containing inhibitors of important receptors.
There are several examples of transamidation currently in the literature. Descriptions of these methods can be found, for example, in U.S. Pat. No. 4,018,747 to Malz et al., U.S. Pat. No. 5,395,974 to McKinney, and U.S. Pat. No. 5,302,756 to McKinney, each of which is incorporated herein. While the reactions described in these patents provide methods to manipulate polyamides, the reactions all suffer from certain shortcomings. These shortcomings include the high levels of ammonia used to drive the reaction, reaction temperatures exceeding 300° C., and reaction pressures well above atmospheric pressure. Also, none of these patents describe the manipulation of small organic molecules, nor do they involve amide metathesis.
Consequently, there is an unmet need for a method that allows the manipulation of polyamides, as well as small carboxamide-containing molecules, which does not suffer from these shortcomings. There is also a need for a method capable of producing carboxamide-containing molecules and polyamide compounds of suitable quality for experimental research and commercial production.